Ascorbic acid may not be involved in cryptochrome-based magnetoreception

Abstract

Seventeen years after it was originally suggested, the photoreceptor protein cryptochrome remains the most probable host for the radical pair intermediates that are thought to be the sensors in the avian magnetic compass. Although evidence in favour of this hypothesis is accumulating, the intracellular interaction partners of the sensory protein are still unknown. It has been suggested that ascorbate ions could interact with surface-exposed tryptophan radicals in photoactivated cryptochromes, and so lead to the formation of a radical pair comprised of the reduced form of the flavin adenine dinucleotide cofactor, FAD• , and the ascorbate radical, Asc shown that ascorbate ions are expected to bind near the tryptophan radicals for periods of a few nanoseconds. The rate at which these encounters happen is low, and it is therefore concluded that ascorbate ions are unlikely to be involved in magnetoreception if the ascorbate concentration is only on the order of 100 M or less.3

Molecular dynamics simulations disclose early stages of the photo-activation of cryptochrome 4

“…Furthermore, here we focus on a radical pair state that is formed in a photo-induced electron transfer reaction from the dark-state protein containing the FAD cofactor in the fully oxidized form. It is currently unknown and intensely debated whether this state could form the basis of a magnetic compass [10,12,25,35,43,[76][77][78]. Some evidence in favour of the alternative radical pair resulting from the re-oxidation of the fully reduced cryptochrome by e.g.…”

“…According to this model, magnetoreception is the result of the quantum coherent evolution of the singlet and triplet states of transient pairs of radicals under the influence of spin-selective reactions and magnetic interactions [6]. Ritz, Adem and Schulten were the first to speculate that the underlying radical pair could be formed by photo-excitation in the animals' eyes in cryptochromes [7], a class of blue-light sensitive flavo-proteins that shares some similarity with photolyases [8]; this supposition still applies; to date, cryptochromes are the only vertebrate proteins known to form radical pairs in a physiologically significant photoreaction and their relevancy to magnetoreception has indeed been implicated in a multitude of studies [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]. The reader is referred to the many reviews on this subject for a more detailed exposition [6,23,[25][26].…”

“…In chickens, this radical can be further photo-reduced to FADHin a process that likely involves intermittent FADH • [28]. It is currently unknown whether the direct photo-reduction of FAD or the dark-state re-oxidation of the fully reduced flavin, FADH -, gives rise to the magnetosensitive radical pair underpinning the compass sensor [10,12,25,35]. Some evidence in favour of the reoxidation hypothesis has become available recently [14,22,[36][37][38][39][40][41].…”

Upper bound on the biological effects of 50/60 Hz magnetic fields mediated by radical pairs

“…The only other radical discussed in the context of magnetoreception is that formed by oxidation of ascorbic acid, Asc  . [FAD  Asc  ] is predicted to show magnetic field effects larger than [FAD  TrpH + ] but smaller than [FAD  Z  ] (45,46,67). In short, it is difficult to imagine a biologically plausible radical pair whose hyperfine couplings make it significantly more sensitive to weak magnetic fields than the simplified model of [FAD  TrpH + ] we have considered here.…”

Molecular dynamics simulations disclose early stages of the photo-activation of cryptochrome 4

“…Ritz, Adem and Schulten were the first to speculate that the underlying radical pair could be formed by photo-excitation in the animals' eyes in cryptochromes [11], a class of blue-light sensitive flavo-proteins that shares some similarity with photolyases [12]; this supposition still applies;. To date, cryptochromes are the only vertebrate proteins known to form radical pairs in a physiologically significant photoreaction and their relevancy to magnetoreception has indeed been implicated in a multitude of studies [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]. The reader is referred to the many reviews on this subject for a more detailed exposition [10,27,29,30].…”